71 Estimation of incidence of MIS-C in Cape Town, South Africa

Abstract Background Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after SARS-CoV-2 infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide. Methods A cohort of children with MIS-C and healthy children was recruited from May 2020 to May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed. Results Sixty-eight children with MIS-C were recruited with a median age of 7 years and 97 healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 SARS-COV-2 infections in children under 14 years old in the city at that time. Black children were over-represented in the MIS-C group (62% vs 37%, p = 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). Median levels of haemoglobin, sodium, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen), neutrophil and white cell count were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety-four point one per cent patient received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. ICU admission was required in 39.7% patient while 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. The median hospital stay duration was 7 days with no deaths. Conclusion The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment. Implications To our knowledge, these are the first data on MIS-C in Africa. This shows that children in Africa are indeed presenting with MIS-C which will increase surveillance around the continent.


Background
Kawasaki disease (kDa) is a multisystemic vasculitis affecting medium and small vessels with a predilection for the coronary arteries. It appears to be very similar to the pediatric multisystemic inflammatory syndrome (PIMS), which is a post-infectious inflammatory condition occurring after SARS-COV2 infection. Although these two entities have clinical and biological similarities, marked differences are identified. The aim of this study is to compare the two conditions in order to highlight the specific criteria of each of these related entities and to describe their demographic, clinical, biological and therapeutic characteristics in our context. Method Single center prospective observational study from January 2021 to March 2022 was conducted, comparing children admitted for PIMS on the basis of persistent fever, inflammatory syndrome, and positive COVID-19 IgG serology to patients hospitalized for kDa according to American Heart Association criteria. Results 42 cases were recruited, among them 24 PIMS and 18 kDa, with a male predominance. The average age was 5 years for PIMS and 2 years and 7 months for kDa. All had a persistant fever with an average duration of 8 days as reason for consultation. Conjunctivitis was found in 88% of kDa vs 75% of PIMS and cheilitis in 94% of kDa vs 75% of PIMS. Skin rash, extremity involvement, cervical adenopathy were reported in both pathologies with respective percentages of 62.5%, 17.4% and 25% for PIMS vs 61.1%, 33.3% and 33.3% for kDa. Abdominal pain was reported in 54.2% of PIMS patients vs 5.6% of kDa. All patients had an inflammatory syndrome. The mean sedimentation rate was 67 mm at the first h in PIMS and 99 mm at the first h in kDa. The mean CRP was 147 mg/l in PIMS vs 132 mg/l in kDa. Lymphopenia was predominant in PIMS with 33% vs 11% in kDa. Cardiac enzymes were higher in PIMS with 29% of myocarditis and 15% of coronary dilatation vs 16.7% of coronary involvement in kDa. All PIMS patients received immunoglobulin infusion IV-IG, corticosteroid therapy, and an antiplatelet agent, whereas patients with kDa received IV-IG and acetyl salicylic acid in anti-inflammatory doses. Apyrexia was obtained at day 1 of treatment in the majority of patients, whereas 5.6% of kDa had persistent aneurysm. Conclusion PIMS cases predominated over kDa cases during this pandemic period. The distinction between the two entities could be difficult given the clinico-biological similarities. Abdominal pain was significantly more frequent in PIMS patients, whereas lymphopenia and myocarditis were not. The prognosis was better in PIMS.

Background
Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after SARS-CoV-2 infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide. Methods A cohort of children with MIS-C and healthy children was recruited from May 2020 to May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed.

Results
Sixty-eight children with MIS-C were recruited with a median age of 7 years and 97 healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 SARS-COV-2 infections in children under 14 years old in the city at that time. Black children were over-represented in the MIS-C group (62% vs 37%, p ¼ 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). Median levels of haemoglobin, sodium, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen), neutrophil and white cell count were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety-four point one per cent patient received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. ICU admission was required in 39.7% patient while 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. The median hospital stay duration was 7 days with no deaths.

Conclusion
The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment. Implications To our knowledge, these are the first data on MIS-C in Africa. This shows that children in Africa are indeed presenting with MIS-C which will increase surveillance around the continent.

Background
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, shock, rash, abdominal pain and raised inflammatory markers, as well as common features of inflammatory childhood illnesses. In the acute setting, especially in countries where infectious diseases are common differential diagnoses, it is challenging to diagnose MIS-C. Therefore, data differentiating MIS-C from other inflammatory and/or febrile diseases at presentation is needed. Methods Prospective data was collected from children admitted to the Red Cross War Memorial Children's Hospital in Cape Town, South Africa from May 2020 to end November 2021 where MIS-C was part of their differential diagnoses. Clinical features on the day of admission were compared between children with confirmed MIS-C (MIS-Cþ) and those with alternate diagnoses (MIS-C-).

Results
In this time period, 60 children were MIS-Cþ and 34 were MIS-C-. There was no significant difference in age (p ¼ 0.321), sex (p ¼ 0.525), ethnicity (p ¼ 0.279), or in the frequency of comorbidities (p ¼ 0.151) between the two groups. The presence of conjunctivitis (OR ¼ 8.12), rash (OR ¼ 8.67), tachycardia (OR ¼ 2.8) and oral mucositis (OR ¼ 3.75) was associated with MIS-Cþ while abdominal pain and hypotension were not. MIS-Cþ had statistically higher median C-reactive protein (CRP), pro-brain natriuretic protein (pro-BNP) and ferritin, and lower median lymphocyte count, platelet count and sodium levels than MIS-C-. Ferritin discriminated MIS-Cþ well (AUC ¼ 0.86) with a 94% sensitivity and 60% specificity at a cut off of > 195ng/l. Sodium had an AUC of 0.72, with a 70% sensitivity and 71% specificity at a cut off of < 132.5 mmol/l. CRP did not distinguish MIS-C well (AUC ¼ 0.52) and although they had good AUC, platelet count and pro-BNP had cut off values in the normal range decreasing clinical utility.

Conclusion
We provide evidence for the use of accessible clinical and laboratory variables for the diagnosis of MIS-C in diverse settings.

Implications
These data will aid clinicians to do a rapid diagnosis (and ultimately treat earlier) of patients with MIS-C in the acute setting, especially those in under-resourced settings. 72  Background Primary dysautonomia is a disorder of the autonomic nervous system with nonspecific manifestations, mainly affecting blood pressure and heart rate.

Objective
We report the diagnostic odyssey in an 11-year-old girl starting with arthralgia and leading to the final diagnosis of a rare dysautonomia.

Methods
A 13-year-old girl, with no pathologic history, was admitted to pediatrics for diffuse arthralgia without clinical inflammatory signs. Biological exploration unmasked a morning proteinuria without hypoalbuminemia and with a normal electrophoretic profile, microcytic anaemia and orthostatic hypotension authenticated during his hospitalization. Exhaustive explorations were undertaken (including autoimmune panel, ophthalomological examination, full metabolic screen and even renal biopsy), without any conclusive result.

Results
The development-after one year of follow up-of arterial hypertension, associated with orthostatic hypotension and proteinuria, points toward the extremely rare defect in baroreceptors. The management, in collaboration with the cardiology department, enhanced the patient's quality of life with a reduction in hypertensive peaks. An appropriate lifestyle also amended the intensity of orthostatic hypotension. The close multidisciplinary follow-up over >48 months is reassuring.

Conclusion
The peculiar baroreceptor defect in a context of dysautonomia should be kept in mind in the (long) list of differential diagnosis of arthralgias, as joint pain can be triggered by dysautonomia. Management is mainly symptomatic.